ABSTRACT
To elucidate pathogenic molecules in keloids, microarray analysis was performed using RNAs extracted from keloid-derived fibroblasts and normal skin-derived fibroblasts from the same patient with a typical keloid. Among 11 up-regulated extracellular matrix genes, cartilage oligomeric matrix protein (COMP) was most prominently increased. Up-regulation of COMP mRNA and protein was confirmed in the keloid tissue by quantitative RT-PCR and Western blot. Using immunohistochemistry, we compared 15 keloids and 6 control normal tissues using a COMP-specific antibody and found that COMP stained positively in 10 keloids (66.7%), whereas no staining was observed in normal tissues, demonstrating the ectopic expression of COMP in keloids. Comparing keloids smaller or larger than 10 cm(2), the larger keloids were significantly more intensely stained with the COMP-specific antibody. Because COMP reportedly accelerates collagen type I fibril assembly, we examined whether extracellular type I collagen deposition is altered by silencing COMP mRNA by small interfering RNA (siRNA). Immunocytochemistry showed at 96 hours after transfection with COMP siRNA that the extracellular deposition of type I collagen was decreased compared to that observed with control siRNA. Further, COMP knockdown decreased amount collagens type I to V in the medium and on the cell surfaces. Our data suggest that COMP facilitates keloid formation by accelerating collagen deposition, thus providing a new therapeutic target.
Subject(s)
Extracellular Matrix Proteins/metabolism , Glycoproteins/metabolism , Keloid/metabolism , Keloid/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Cartilage Oligomeric Matrix Protein , Child , Child, Preschool , Collagen Type I/metabolism , Dermis/drug effects , Dermis/pathology , Extracellular Matrix Proteins/genetics , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/pathology , Gene Expression Profiling , Gene Expression Regulation/drug effects , Glycoproteins/genetics , Humans , Immunohistochemistry , Keloid/genetics , Male , Matrilin Proteins , Middle Aged , Oligonucleotide Array Sequence Analysis , RNA, Small Interfering/metabolism , Transforming Growth Factor beta1/pharmacology , Young AdultSubject(s)
Gene Expression Regulation , Intracellular Signaling Peptides and Proteins/metabolism , Keloid/metabolism , Adult , Aged , Aged, 80 and over , DNA Primers/genetics , Female , Fibroblasts/cytology , Humans , In Vitro Techniques , LIM Domain Proteins , Male , Middle Aged , Models, Biological , Protein Structure, Tertiary , Receptors, Transforming Growth Factor beta/metabolism , Signal Transduction , Skin/cytology , Transcription, Genetic , Transforming Growth Factor beta/metabolismABSTRACT
BACKGROUND: Frontal fibrosing alopecia (FFA) is characterized by frontotemporal hair recession and eyebrow loss and by a histopathology identical to lichen planopilaris. Differential diagnosis from other types of alopecia, including alopecia areata (AA), is necessary in some cases. OBJECTIVE: To describe dermoscopic findings of FFA and to investigate the possibility of utilizing dermoscopy as a diagnostic tool for FFA. METHODS: Four cases of FFA diagnosed by clinical and/or histological findings were examined by dermoscopy. RESULTS: The loss of orifices, perifollicular erythema or scale was seen in all the four cases (4/4), in three cases (3/4) or in two cases (2/4), respectively. None of the cases showed yellow dots characteristic of AA. Immunohistochemistry showed T lymphocyte infiltration into the infundibulum and isthmus. CONCLUSION: Dermoscopy is a helpful diagnostic tool for FFA especially to distinguish it from AA.
